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The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

Moral R, Wang R, Russo IH, Mailo DA, Lamartiniere CA, Russo J - BMC Genomics (2007)

Bottom Line: BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues.BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages.By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals.

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Affiliation: Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Raquel.Moral@uab.es

ABSTRACT

Background: Phthalate esters like n-butyl benzyl phthalate (BBP) are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2-20) to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days).

Results: Here we show that exposure to BBP increased the uterine weight/body weight ratio at 21 days and decreased the body weight at time of vaginal opening. BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic profile of the mammary gland mainly at the end of the exposure (21 days), becoming less prominent thereafter. By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals.

Conclusion: These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

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Related in: MedlinePlus

Proliferative index analyses of the mammary gland. A: Immunohistochemical detection of BrdU incorporation in proliferating cells (brown cells) in the epithelial structures TEB, TD and ducts, AB and Lob1. Olympus BX40 microscope with 40× objective. B: Proliferative index (mean ± SEM) in each epithelial structure at 21, 35, 50 and 100 days of age. *: significantly different compared to control group (p < 0.05).
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Figure 1: Proliferative index analyses of the mammary gland. A: Immunohistochemical detection of BrdU incorporation in proliferating cells (brown cells) in the epithelial structures TEB, TD and ducts, AB and Lob1. Olympus BX40 microscope with 40× objective. B: Proliferative index (mean ± SEM) in each epithelial structure at 21, 35, 50 and 100 days of age. *: significantly different compared to control group (p < 0.05).

Mentions: BrdU incorporation into the DNA was used as an index of cell proliferation (Figure 1). TEB from BBP exposed rats had significantly (p < 0.05) higher proliferation index than controls by 35 days, whereas in TD and AB the differences were not significant. The proliferative index of Lob1 from controls increased from 35 to 50 days and decreased at 100 days, while in BBP exposed rats this structure showed maximum index of proliferation at 35 days and decreased thereafter, showing significant differences when compared to controls at all these ages (Figure 1).


The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

Moral R, Wang R, Russo IH, Mailo DA, Lamartiniere CA, Russo J - BMC Genomics (2007)

Proliferative index analyses of the mammary gland. A: Immunohistochemical detection of BrdU incorporation in proliferating cells (brown cells) in the epithelial structures TEB, TD and ducts, AB and Lob1. Olympus BX40 microscope with 40× objective. B: Proliferative index (mean ± SEM) in each epithelial structure at 21, 35, 50 and 100 days of age. *: significantly different compared to control group (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200869&req=5

Figure 1: Proliferative index analyses of the mammary gland. A: Immunohistochemical detection of BrdU incorporation in proliferating cells (brown cells) in the epithelial structures TEB, TD and ducts, AB and Lob1. Olympus BX40 microscope with 40× objective. B: Proliferative index (mean ± SEM) in each epithelial structure at 21, 35, 50 and 100 days of age. *: significantly different compared to control group (p < 0.05).
Mentions: BrdU incorporation into the DNA was used as an index of cell proliferation (Figure 1). TEB from BBP exposed rats had significantly (p < 0.05) higher proliferation index than controls by 35 days, whereas in TD and AB the differences were not significant. The proliferative index of Lob1 from controls increased from 35 to 50 days and decreased at 100 days, while in BBP exposed rats this structure showed maximum index of proliferation at 35 days and decreased thereafter, showing significant differences when compared to controls at all these ages (Figure 1).

Bottom Line: BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues.BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages.By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Raquel.Moral@uab.es

ABSTRACT

Background: Phthalate esters like n-butyl benzyl phthalate (BBP) are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2-20) to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days).

Results: Here we show that exposure to BBP increased the uterine weight/body weight ratio at 21 days and decreased the body weight at time of vaginal opening. BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic profile of the mammary gland mainly at the end of the exposure (21 days), becoming less prominent thereafter. By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals.

Conclusion: These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

Show MeSH
Related in: MedlinePlus